DESCRIPTION (Applicant's abstract):Systemic vascular resistance (SVR) increase with advancing age even in healthy humans. Augmented vasoconstriction in the limb vasculature contributes to the age-related elevation in SVR and thus, an elevated sympathetic alpha-adrenergic vasoconstrictor tone could be a mechanism contributing to the increase in SVR with age. The primary aim of the present proposal is to test the hypothesis that tonic increases in sympathetic alpha-adrenergic vasoconstriction contribute to the elevation in limb vascular resistance with age. To address this aim, arterial blood pressure, femoral (whole-leg) blood flow (high resolution ultrasonography), and plasma catecholamines will be determined under resting baseline conditions and after local alpha-adrenergic blockade (intra-arterial infusions of phentolamine). Other measurements will include muscle sympathetic nerve activity (microneurography), leg tissue mass (DEXA), and femoral artery structure (ultrasound). The results of the proposed study should provide new and clinically important information concerning the role of sympathetic-adrenergic mechanisms in age-related elevations in limb vascular resistance.